text: The most common clinical usage of additive effect in pharmacology is combination therapy. Two or more therapeutic agents are used in combination therapy to treat a single disease. Different drugs in the same combination therapy act on different biological and biochemical pathways in the body to produce an additive effect.
  An example of combination therapy demonstrating additive effect is the use of β-2 adrenergic receptor agonists together with inhaled corticosteroids. This is a treatment for two commonly seen pulmonary diseases, asthma and chronic obstructive pulmonary disease. β-2 adrenergic receptor agonists act as bronchodilators, having an effect of inducing bronchodilation to relieve bronchoconstriction; Inhaled corticosteroids act as anti-inflammatory drugs to decrease the inflammatory response. The two drugs act on different sites in the body. The corticosteroids also reverse and restore the function and number of β-2 adrenergic receptors in patients’ lungs in vivo. Meanwhile, the combined activity of two drugs resolves the problem of reduced sensitivity in some patients with chronic obstructive pulmonary disease towards inhaled corticosteroids. A common drug from this example can be found is Seretide®, containing a long-acting β-2 adrenergic receptor agonist named as Salmeterol and a corticosteroid named as Fluticasone.
  Additive interaction can also be found in combination therapy for treating hypertension. The combination of angiotensin II receptor blockers (ARBs) and calcium channel blockers (CCBs) is one of the suggested antihypertensive therapies. ARBs inhibit the action of angiotensin II to decrease fluid retention and blood volume to decrease blood pressure, reduce vasoconstriction to decrease peripheral vascular resistance, and prevent vascular fibrosis to decrease vascular stiffness. CCBs are vasodilators inhibiting L-type voltage-operated calcium channels in the blood vessels to alleviate vasoconstriction resulting in a decrease in peripheral vascular resistance. The two types of drugs act on different pathways to produce an additive effect on lowering blood pressure without any increase in adverse effects. This combination, with ARB, valsartan, and CCB, amlodipine, is a common treatment in high-risk hypertensive patients, especially the elderly.
  The treatment for another common disease, primary hypercholesterolemia, also demonstrates additive effect. Plant sterol-ester margarine and a common type of antihyperlipidaemic drug, cerivastatin, have an additive effect in reducing LDL cholesterol, without significant interaction between the two drugs. Another drug combination with additive effect for hypercholesterolemia is niacin (vitamin B3) and simvastatin. This drug combination is also known as Simcor commercially. Niacin can reduce the secretion of LDL cholesterol and very-low-density lipoprotein cholesterol (VLDL cholesterol). On the other hand, simvastatin can reduce the synthesis of LDL cholesterol and triglycerides, and increase the level of high-density lipoprotein cholesterol (HDL cholesterol). Together, niacin and simvastatin reduce the level of LDL cholesterol and increases the level of HDL cholesterol, therefore managing hypercholesterolemia effectively.